Methylglyoxal Augments Angiotensin II–Induced Contraction in Rat Isolated Carotid Artery
Abstract.: Methylglyoxal (MGO), a metabolite of glucose, accumulates in vascular tissues of a hypertensive animal. In the present study, we examined the effect of MGO on angiotensin (Ang) II–induced contraction of rat carotid artery. Treatment of carotid artery with MGO (420 μM, 30 min) significantl...
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| Format: | Article |
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Elsevier
2010-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319308175 |
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| author | Masashi Mukohda Hideyuki Yamawaki Muneyoshi Okada Yukio Hara |
| author_facet | Masashi Mukohda Hideyuki Yamawaki Muneyoshi Okada Yukio Hara |
| author_sort | Masashi Mukohda |
| collection | DOAJ |
| description | Abstract.: Methylglyoxal (MGO), a metabolite of glucose, accumulates in vascular tissues of a hypertensive animal. In the present study, we examined the effect of MGO on angiotensin (Ang) II–induced contraction of rat carotid artery. Treatment of carotid artery with MGO (420 μM, 30 min) significantly augmented Ang II (0.1 to 30 nM)–induced concentration-dependent contraction. The effect was abolished by the removal of endothelium. BQ-123 (1, 5 μM), an endothelin A– receptor blocker, had no effect on the MGO-induced enhancement of Ang II–induced contraction. AL8810 (1 μM), a prostaglandin F2α–receptor blocker, or SQ29548 (1 μM), a thromboxane A2– receptor blocker, was also ineffective. However, tempol (10 μM), a superoxide scavenger, and catalase (5000 U/mL), which metabolizes hydrogen peroxide to water, significantly prevented the effect of MGO. Combined MGO and Ang II treatment increased reactive oxygen species (ROS) production. Apocynin (10 μM) or gp91ds-tat (3 μM), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, significantly prevented the effect of MGO. Gp91ds-tat or an Ang II type 1–receptor (AT1R) blocker, losartan (10 μM), prevented the MGO-mediated increased ROS production. The present study revealed that MGO augments Ang II–induced contraction by increasing AT1R-mediated NADPH oxidase–derived superoxide and hydrogen peroxide production in endothelium of rat carotid artery. Keywords:: glucose metabolite, vascular endothelium, angiotensin, reactive oxygen species, smooth muscle contractility |
| first_indexed | 2024-12-13T14:21:07Z |
| format | Article |
| id | doaj.art-628acbc846034b27b6163bc876bbf5d0 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-13T14:21:07Z |
| publishDate | 2010-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-628acbc846034b27b6163bc876bbf5d02022-12-21T23:42:06ZengElsevierJournal of Pharmacological Sciences1347-86132010-01-011144390398Methylglyoxal Augments Angiotensin II–Induced Contraction in Rat Isolated Carotid ArteryMasashi Mukohda0Hideyuki Yamawaki1Muneyoshi Okada2Yukio Hara3Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, JapanLaboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, Japan; Corresponding author. yamawaki@vmas.kitasato-u.ac.jpLaboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, JapanLaboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, JapanAbstract.: Methylglyoxal (MGO), a metabolite of glucose, accumulates in vascular tissues of a hypertensive animal. In the present study, we examined the effect of MGO on angiotensin (Ang) II–induced contraction of rat carotid artery. Treatment of carotid artery with MGO (420 μM, 30 min) significantly augmented Ang II (0.1 to 30 nM)–induced concentration-dependent contraction. The effect was abolished by the removal of endothelium. BQ-123 (1, 5 μM), an endothelin A– receptor blocker, had no effect on the MGO-induced enhancement of Ang II–induced contraction. AL8810 (1 μM), a prostaglandin F2α–receptor blocker, or SQ29548 (1 μM), a thromboxane A2– receptor blocker, was also ineffective. However, tempol (10 μM), a superoxide scavenger, and catalase (5000 U/mL), which metabolizes hydrogen peroxide to water, significantly prevented the effect of MGO. Combined MGO and Ang II treatment increased reactive oxygen species (ROS) production. Apocynin (10 μM) or gp91ds-tat (3 μM), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, significantly prevented the effect of MGO. Gp91ds-tat or an Ang II type 1–receptor (AT1R) blocker, losartan (10 μM), prevented the MGO-mediated increased ROS production. The present study revealed that MGO augments Ang II–induced contraction by increasing AT1R-mediated NADPH oxidase–derived superoxide and hydrogen peroxide production in endothelium of rat carotid artery. Keywords:: glucose metabolite, vascular endothelium, angiotensin, reactive oxygen species, smooth muscle contractilityhttp://www.sciencedirect.com/science/article/pii/S1347861319308175 |
| spellingShingle | Masashi Mukohda Hideyuki Yamawaki Muneyoshi Okada Yukio Hara Methylglyoxal Augments Angiotensin II–Induced Contraction in Rat Isolated Carotid Artery Journal of Pharmacological Sciences |
| title | Methylglyoxal Augments Angiotensin II–Induced Contraction in Rat Isolated Carotid Artery |
| title_full | Methylglyoxal Augments Angiotensin II–Induced Contraction in Rat Isolated Carotid Artery |
| title_fullStr | Methylglyoxal Augments Angiotensin II–Induced Contraction in Rat Isolated Carotid Artery |
| title_full_unstemmed | Methylglyoxal Augments Angiotensin II–Induced Contraction in Rat Isolated Carotid Artery |
| title_short | Methylglyoxal Augments Angiotensin II–Induced Contraction in Rat Isolated Carotid Artery |
| title_sort | methylglyoxal augments angiotensin ii induced contraction in rat isolated carotid artery |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319308175 |
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